Top

Published in:

01-04-2022 | Spastic Paraplegia | Brief Communication

A case of spastic paraplegia type 11 mimicking a GM2-gangliosidosis

Authors: Diego Lopergolo, Gianna Berti, Francesca Mari, Enrico Bertini, Alessandra Rufa, Carla Battisti, Francesco Sicurelli, Alessandra Renieri, Antonio Federico, Konrad Sandhoff, Alessandro Malandrini

Published in: Neurological Sciences | Issue 4/2022

Abstract

Introduction

Spastic paraplegia type 11 (SPG11) is the most frequent autosomal recessive HSP. Studies on SPG11 patients’ fibroblasts, post-mortem brains, and mouse models revealed endolysosomal system dysfunction and lipid accumulation, especially gangliosides. We report a patient with early clinical findings mimicking a GM2-gangliosidosis.

Methods

A clinical, biochemical, and metabolic characterization was performed. Electron microscopy analysis was completed on rectal mucosa and skin biopsy specimens. A NGS panel of genes associated to neuronal ceroid lipofuscinosis and HSP was analyzed.

Results

The patient presented with worsening walking difficulty and psychomotor slowdown since childhood; to exclude a neurometabolic storage disease, skin and rectal biopsies were performed: enteric neurons showed lipofuscin-like intracellular inclusions, thus suggesting a possible GM2-gangliosidosis. However, further analysis did not allow to confirm such hypothesis. In adulthood we detected flaccid paraplegia, nystagmus, axonal motor neuropathy, carpus callosum atrophy, and colon atony. Surprisingly, the NGS panel detected two already reported SPG11 mutations in compound heterozygosity.

Conclusions

We describe for the first time pathological hallmarks of SPG11 in enteric neuron from a rectal mucosa biopsy. The report illustrates the possible overlap between SPG11 and GM2-gangliosidosis, especially in the first disease phases and helps to improve our knowledge about SPG11 physiopathology.

Stevanin G, Azzedine H, Denora P et al (2008) Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain 131(3):772–784. https://doi.org/10.1093/brain/awm293CrossRefPubMed

Pérez-Brangulí F, Mishra HK, Prots I et al (2014) Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia. Hum Mol Genet 23(18):4859. https://doi.org/10.1093/HMG/DDU200CrossRefPubMedPubMedCentral

Renvoisé B, Chang J, Singh R et al (2014) Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11. Ann Clin Transl Neurol 1(6):379. https://doi.org/10.1002/ACN3.64CrossRefPubMedPubMedCentral

Branchu J, Boutry M, Sourd L et al (2017) Loss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration. Neurobiol Dis 102:21. https://doi.org/10.1016/J.NBD.2017.02.007CrossRefPubMedPubMedCentral

Denora PS, Smets K, Zolfanelli F et al (2016) Motor neuron degeneration in spastic paraplegia 11 mimics amyotrophic lateral sclerosis lesions. Brain 139(6):1723–1734. https://doi.org/10.1093/brain/aww061CrossRefPubMedPubMedCentral

Boutry M, Branchu J, Lustremant C et al (2018) Inhibition of lysosome membrane recycling causes accumulation of gangliosides that contribute to neurodegeneration. Cell Rep 23(13):3813. https://doi.org/10.1016/J.CELREP.2018.05.098CrossRefPubMed

Breiden B, Sandhoff K (2020) Mechanism of secondary ganglioside and lipid accumulation in lysosomal disease. Int J Mol Sci 21(7). https://doi.org/10.3390/IJMS21072566

Stevanin G, Santorelli FM, Azzedine H et al (2007) Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet 39(3):366–372. https://doi.org/10.1038/ng1980CrossRefPubMed

Giannoccaro MP, Liguori R, Arnoldi A, Donadio V, Avoni P, Bassi MT (2014) Atypical late-onset hereditary spastic paraplegia with thin corpus callosum due to novel compound heterozygous mutations in the SPG11 gene. J Neurol 261(9):1825–1827. https://doi.org/10.1007/s00415-014-7443-3CrossRefPubMed

10.

Masingue M, Dufour L, Lenglet T et al (2020) Natural history of adult patients with GM2 gangliosidosis. Ann Neurol 87(4):609–617. https://doi.org/10.1002/ana.25689CrossRefPubMed

11.

Jain A, Kohli A, Sachan D (2010) Infantile Sandhoff’s disease with peripheral neuropathy. Pediatr Neurol 42(6):459–461. https://doi.org/10.1016/j.pediatrneurol.2010.02.007CrossRefPubMed

12.

Kollmann K, Uusi-Rauva K, Scifo E, Tyynelä J, Jalanko A, Braulke T (2013) Cell biology and function of neuronal ceroid lipofuscinosis-related proteins. Biochim Biophys Acta Mol Basis Dis 1832(11):1866–1881. https://doi.org/10.1016/j.bbadis.2013.01.019CrossRef

Title: A case of spastic paraplegia type 11 mimicking a GM2-gangliosidosis
Authors: Diego Lopergolo
Gianna Berti
Francesca Mari
Enrico Bertini
Alessandra Rufa
Carla Battisti
Francesco Sicurelli
Alessandra Renieri
Antonio Federico
Konrad Sandhoff
Alessandro Malandrini
Publication date: 01-04-2022
Publisher: Springer International Publishing
Keywords: Spastic Paraplegia
Nystagmus
Published in: Neurological Sciences / Issue 4/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-021-05841-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A case of spastic paraplegia type 11 mimicking a GM2-gangliosidosis

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2022

The patient–caregiver dyad: the impact of cognitive and functional impairment

Charcot-Marie-Tooth neuropathy score and ambulation index are both predictors of orthotic need for patients with CMT

Efficacy and safety of erenumab in migraine prevention: evidences from direct and indirect comparisons

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

Risk of migraine contributed by genetic polymorphisms of ANKDD1B gene: a case–control study based on Chinese Han population

The need for a broad differential: intramedullary neurosarcoidosis case report